chr21-34856063-C-T

Variant names:

• chr21-34856063-C-T
• rs2834651
• NM_001754.5:c.613+3411G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001754.5(RUNX1):​c.613+3411G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,128 control chromosomes in the GnomAD database, including 28,820 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (28820 hom., cov: 33)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.542
• Publications: 4 publications found

Genes affected

RUNX1 (HGNC:10471): (RUNX family transcription factor 1) Core binding factor (CBF) is a heterodimeric transcription factor that binds to the core element of many enhancers and promoters. The protein encoded by this gene represents the alpha subunit of CBF and is thought to be involved in the development of normal hematopoiesis. Chromosomal translocations involving this gene are well-documented and have been associated with several types of leukemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RUNX1-AS1 (HGNC:56821): (RUNX1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX1	NM_001754.5	c.613+3411G>A		intron_variant	Intron 6 of 8	ENST00000675419.1	NP_001745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000675419.1	c.613+3411G>A		intron_variant	Intron 6 of 8		NM_001754.5	ENSP00000501943.1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 90037 AN: 152010 Hom.: 28799 Cov.: 33

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.603

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.592 AC: 90086 AN: 152128 Hom.: 28820 Cov.: 33 AF XY: 0.604 AC XY: 44874 AN XY: 74356

African (AFR) AF: 0.333 AC: 13807 AN: 41460

American (AMR) AF: 0.719 AC: 11002 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2101 AN: 3466

East Asian (EAS) AF: 0.873 AC: 4531 AN: 5188

South Asian (SAS) AF: 0.766 AC: 3699 AN: 4828

European-Finnish (FIN) AF: 0.753 AC: 7968 AN: 10584

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44900 AN: 67988

Other (OTH) AF: 0.605 AC: 1276 AN: 2110

Alfa AF: 0.643 Hom.: 70436

Bravo AF: 0.579

Asia WGS AF: 0.770 AC: 2672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.28
DANN	Benign	0.61
PhyloP100		-0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2834651; hg19: chr21-36228360;